Global environmental health concerns can only be addressed through the cooperative actions of multiple countries and institutions, but this requires effective leadership and coordination. The International Programme on Chemical Safety (IPCS) was established in 1980 as the lead international coordinating body to provide science-based assessments of the potential health risks posed by environmental contaminants. IPCS is managed by the World Health Organization (WHO) but involves many other United Nations, regional, international, national, and non-governmental organizations. IPCS accomplishes most of its work through the efforts of a broad diverse network of internationally recognized scientific experts. The National Institute of Health (NIH)/National Institute of Environmental Health Sciences (NIEHS) played a key role in the formation of IPCS, and NIEHS (intramural and extramural) continues to play a significant leadership role for many IPCS activities. A WHO/IPCS Interregional Research Unit (IRRU) is located on the NIEHS campus to implement the activities supported by the NIEHS-WHO Cooperative Agreement, which addresses the following global cross-cutting environmental health issues: 1) children's health and the environment;2) toxicogenomics/gene-environment interactions/biomarkers;3) persistent toxic substances and endocrine disruptors;4) improved risk assessment methodologies;and 5) development of an integrated risk assessment approach with an emphasis on mixtures. A prototype, step-wise implementation strategy, shown to work very effectively has been developed to implement these aims. This strategy combines a regional approach with a flexible, modular process that allows for uncertainties of unforeseen scientific opportunities, generates unique scientific knowledge, and ultimately leads to the collaboration of research among scientists in developing and developed countries. In addition, this strategy has served as a catalyst for additional multi-partner support and collaborative actions. The activities supported by the Cooperative Agreement result in numerous publications, training of scientists and health care professionals, collaborative research opportunities, generation of unique scientific information and initiation of data collection archives, education, awareness raising, and information dissemination. Countries use these products to put in place evidence based public health, prevention, and remediation policies at the national and regional level.